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2. This is an important question since even now marketing authorization constitutes the

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so, on certain conditions, if the particulars for the relief of atopic eczema. I3 It also pos- are drawn up in accordance with the sesses two authorizations granted in 1990 for abridged procedure. 9 Epogam in paediatric capsules and for a product called 'Efamast', indicated for the relief of mastalgia. 14 The normal procedure was followed in the applications for those three authorizations. Accordingly, Scotia had to satisfy all the requirements laid down by 3. As regards the United Kingdom legisla- Community law. The tests and clinical trials tion, the Medicines Act 1968 (hereinafter 'the began in 1979 and by 1990 a considerable 1968 Act') makes provision for the licensing amount had been spent on research (about authority (the Secretary of State for Health) £19 million). I5 and lays down rules for the procedure to be followed in the preliminary stages of an application for marketing authorization, 10 and for the grant, renewal or refusal of such authorization. n

4. The question whether those provisions 6. In 1992 the MCA granted Norgine autho- are compatible with Community law has rization to put a medicinal product called been raised in proceedings between Scotia 'Unigam' 1 6 on the United Kingdom market. Pharmaceuticals Limited (hereinafter The application was dealt with under the 'Scotia'), the plaintiff in the main action, and 'abridged procedure' by detailed references the Medicines Control Agency (hereinafter to published scientific literature. '7 'the M C A ' ) , i 2 in which Scotia alleges that the M C A used the abridged procedure and unjustifiably relaxed the conditions for the grant of marketing authorization in favour of Norgine Limited (hereinafter 'Norgine'), a company in competition with Scotia.

9. The essential aim of the Community leg- islature is still that set forth by Advocate General Mancini in his Opinion in Case 301/82 Clin-Midy v Belgium [1984] ECR 10. According to the plan drawn u p as far 251. 2° I shall repeat it verbatim: back as 1965, the Community legislature has in successive stages 22 used legal procedures in pursuit of these various objectives:

'The aim of the directive [65/65] is defined in the preamble. The first recital lays down the basic principle on which any rule con- cerning the production and distribution of proprietary medicinal products must be — the social and economic context 23 of the based: its "primary purpose ... must be to medicinal product is taken into account safeguard public health". That principle is by Directive 87/21; then developed. In particular, the directive states that: (a) that objective must be attained by means which will not hinder the develop- 21 — Opinion, p. 262. ment of the pharmaceutical industry or trade 22 — The adverb 'progressively' suggests the idea of gradual development in stages and is continually referred to in sub- sequent Community measures: seventh recital in the pream- ble to Directive 75/318, fifth recital in the preamble to Directive 75/319 and first recital in the preamble to Direc- tive 87/19. 18 — Observations of the United Kingdom, point 15, and Obser- 23 — Referred to in the second recital in the preamble to Direc- vations of the Commission, point 3. tive 65/65: '... this objective must be attained by means 19 — Observations of the Commission, point 3. which will not hinder the development of the pharmaceuti- 20 — See Opinion and paragraphs 5 to 7 of the judgment. cal industry ...'

24 — Second recital in the preamble to Directive 65/65: '... or trade in medicinal products within the Community ..." 30 — See inter alia: P. Deboysen 'Le Marché Unique des Produits Pharmaceutiques' and 'Développements Récents du Droit 25 — Cited above at footnote 6, in particular the first and second Communautaire relatif aux Médicaments', op. cit.; Vanpe recitals. and Leguen: La Construction de l'Europe Pharmaceutique 26 — Ibid, and see especially the first, second and third recitals. — Le Monier des Douze, Ed. Masson, 1991; M. Cassan: 27 — Cited above at footnote 8, see in particular the first and sec- L'Europe Communautaire de la Santé, Ed. Economica, Collection Coopération et Développement, p. 104; F. ond recitals. Dehousse: 'Le Marché Unique des Produits Pharmaceu- 28 — That objective is constandy reaffirmed in subsequent legis- tiques', Journal des Tribunaux, 1992, N o 5633, p. 383 to lation: first recital in the preamble to Directives 75/319, p. 386; Campion et Víala: *Vers la Libre Circulation des 87/19, 87/21, third recital in the preamble to the standards Médicaments en Europe', Revue de Droit Sanitaire et and protocols directive and fourth recital in the preamble t o Social, N o 1, 1994, pp. 80 to 97. Directive 83/570. 29 — In particular, first and second recitals in the preamble to 31 — Sixth recital in the preamble to Directive 65/65. Directive 65/65. 32 — First recital in the preamble to Directive 65/65.

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14. Between 1975 and 1985, while still pur- before the Court, namely with regard to the suing the primary objective, the legislature grant of marketing authorization under the took into consideration the aim of achieving abridged procedure by detailed references to the free movement of medicinal products. 33 published scientific literature. That objective was treated as complementary to the first. 34

18. The Commission considered the applica- tion of the derogation system and found that some national authorities are very quick to 16. The features which I have sketched in allow use of the abridged procedure and outline can be applied specifically to the case hardly check the references to published data supplied by an applicant for marketing authorization in respect of a generic medici- 33 — First and second recitals in the preamble to the standards nal product. This seriously penalizes a firm and protocols directive, first, second and third recitals in granted marketing authorization in respect the preamble to Directive 75/319 and first and second recit- als in the preamble to Directive 83/570. of an innovatory medicinal product, since 34 — Third recital in the preamble to the standards and protocols the results of the tests it submits in connec- directive, first recital in the preamble to Directive 75/319 and third recital in the preamble to Directive tion with its original application constitute 83/570. more often that not the basis of the dossier 35 — See the completion of the internal market: Commission's White Paper for the attention of the Council [ C O M (85) supplied by an applicant in respect of a 310 final version of 14 June 1985] . generic medicinal product. That is apparent 36 — Second recital in the preamble to Directive 65/65: '... means which will not hinder the development of the pharmaceuti- from the Explanatory Memorandum to the cal industry ...' Commission's report. 40 37 — Second recital in the preamble to Directive 87/21: '... expe- rience has shown that it is advisable to stipulate more pre- cisely the cases in which the results of pharmacological and toxicological tests or clinical trials do not have to be pro- vided with a view to obtaining authorization for a propri- etary medicinal product which is essentially similar to an 39 — Article 1 of Directive 87/21. authorized product, while ensuring that innovative firms are not placed at a disadvantage'. 40 — Explanatory Memorandum [ C O M (84) 437 final version of 25 September 1984] concerning the proposal for a Council 38 — Second recital in the preamble to Directive 87/19: '... in direcave amending Directive 65/65/EEC on the approxima- order to achieve such optimum protection of health, the tion of provisions laid down by law, regulation or adminis- resources allocated to pharmaceutical research must not be trative action relating to proprietary medicinal products, squandered ...' point 14.

20. In this new stage, the Community legis- 21. Since the Community legislature had lature intends to carry its task of harmoniza- allowed proof of the reliability of some tests tion into an area in which the discretionary and experts' reports to be provided by the margin with regard to marketing authoriza- submission of documents, it had to be seen tion enjoyed by the various national author- to be exacting as to the contents of the scien- ities is still too wide. The means used to tific documents to be submitted. avoid any encouragement of disparities between national practices are, first, a stricter limitation on access to that type of pro- cedure and, second, a highly specific and very strict definition of the conditions to be satisfied in order for the abridged pro- cedure 42 to be used. However, the principal aim pursued in taking account of the social and economic context of the medicinal 22. In keeping with the realistic approach which had hitherto guided it, the legislature took account of certain specific and objective factors: 41 — Ibid., point 15. 42 — Second recital in the preamble to Directive 87/21: '... it is advisable to stipulate more precisely the cases in which the results of pharmacological and toxicological tests and clinical trials do not have to be provided ...* 43 — First recital in the preamble to Directive 87/21.

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— the cost of the research and development 24. In the new measure, the legislature

needed to perfect a product of the kind in reaffirms that an application for marketing question; *• authorization under the abridged procedure must fulfil an initial condition in order to be acceptable: the medicinal product concerned 50 must be a generic one; in embodying the principle that the abridged procedure is not to be used where that would prejudice the law relating to the protection of industrial — the performance of tests, which delays and commercial property, 5 1 it adds a further the marketing of a medicinal product and condition for the application to be accepted. shortens the period of exclusive rights granted by the patent. 4 5

. . (i) . . . proprietary medicinal product (. . .) essentially mentary, essential and necessary to the similar to a product authorized . . .; attainment of the ultimate objective. 4 8 (ii) . . . the constituent or constituents of the proprietary medicinal product have a well-established medici nal use, with recognized efficacy and an acceptable level of safety; (iii) . . . proprietary medicinal product (. . .) essentially similar to a product authorized . . .; 44 — The pharmaceutical industry is almost completely self- (b) .

. .' footnote 40, point 14. 52 — Point (a) of the first paragraph of Article 1 of Directive 46 — Second recital in the preamble to Directive 65/65. 87/21: "The applicant shall not be required to provide the results of pharmacological and toxicological tests or the 47 — Two measures concerning certain economic aspects of results of clinical trials if he can demonstrate . . .' medicinal products and intended particularly to meet the pharmaceutical industry's preoccupations have been 53 — Second protocol to the annex to the standards and proto adopted: Council Directive 89/105/EEC of 21 December cols directive concerning pharmacological and toxicological 1988 relating to the transparency of measures regulating the tests, that is to say the effects produced in animals, and pricing of medicinal products for human use and their pharmacodynamic tests, that is to say how the body dis inclusion in the scope of national health insurance systems poses of drugs, as amended by Directives 87/19 and 83/570. (OJ 1989 L 40, p. 8) and Council Regulation (EEC) N o 54 — The third protocol to the annex to the standards and p r o 1768/92 of 18 June 1992 concerning the creation of a sup tocols directive, as amended by Directives 83/570 and plementary protection certificate for medicinal products 87/19, introduces the concept of clinical trials and clinical (OJ 1992 L 182, p. 1). pharmacology to be carnea out on patients receiving the 48. — Commission's Explanatory Memorandum, cited above at new therapy. footnote 40, point 14, and also the first recital in the pream 55 — Article 1, first paragraph, points (a)(1), (ii), (iii) and (b) of ble to Directives 87/19 and 87/21. Directive 87/21.

27. In the case of the second possibility, M 26. The documents to be supplied in con- the legislature gives an extremely precise and nection with the first possibility 62 are in highly restrictive definition of the conditions essence the dossier previously assembled by to be satisfied for the use of the abridged the innovating firm which holds the market- procedure by references to published scien- ing authorization for the original medicinal tific literature. Thus, only experts for the purposes of Directive 75/319 who are required to take account of scientific and technical progress 65 are entitled to: 56 — Within the meaning of Directive 75/319, as amended b y Directive 83/570. 57 — Article 2(c) of Directive 75/319. 58 — Amended by Directives 87/19 and 83/570. 59 — First protocol t o the annex to the standards and protocols directive, as amended by Directives 83/570 and 87/19. Tests t o check and identify the chemical composition of the product. 60 — Article 9a of Directive 65/65, as amended by Directive 83/570: 'After an authorization has been issued, the person responsible for placing the product on the market must, in '... demonstrate ... by detailed references to respect of the control methods provided for in Article 4(7), published scientific literature presented in take account of technical and scientific progress and intro- duce any changes that may be required to enable the pro- accordance with the second paragraph of prietary medicinal product to be checked by means of gen- erally accepted scientific methods. These changes must be accepted by the competent authorities of the Member State concerned.' 61 — Point 8, second paragraph, Article 4, of Directive 65/65 as 63 — Explanatory Memorandum of the Commission, cited above amended, pharmacological and toxicological tests and clin- at footnote 40, point 15. ical trials. 64 — Point 8(a) (ii), second paragraph, Article 4: 'or by detailed 62 — Point 8(a)(i), second paragraph, Article 4: 'either (...) the references to published scientific literature presented in proprietary medicinal product is essentially similar to A accordance with the second paragraph of Article 1 of Direc- product authorized in the country concerned by the appli- tive 75/318/EEC that the constituent or constituents of the cation and ... the person responsible for the marketing of proprietary medicinal product have a well-established the original medicinal product has consented to the phar- medicinal use, with recognized efficacy and an acceptable macological, toxicological or clinical references contained in level of safety'. the file on the original proprietary medicinal product being used for the purpose of examining the application in ques- 65 — Article 9a of Directive 65/65, as amended by Directive tion'. 83/570.

30. In so far as in practice only a medicinal product which has been in use for decades, and whose constituent or constituents have 28. It is the legislature's intention that mini- been subjected to tests detailed at length and mal use should be made of that possibility: 67 commented on in scientific literature, would in actual fact satisfy those requirements, 6 9 the various intermediate objectives comple- mentary to the prime objective pursued b y Community legislation have been complied with. 'This possibility is, in practice, very limited, since, in accordance with the second para- graph of Article 1 of Directive 75/318/EEC, this bibliographical evidence must be sub- mitted in order to correspond "in like man- ner" to the criteria of safety and efficacy in 31. In the third situation, 70 the legislature the annex to that directive.' provides for a period for protecting the data contained in the dossier submitted in the application for marketing authorization in respect of the original medicinal product.

Member States are at liberty not to apply tne abovementioned six- year period beyond the date of expiry of a patent protecting the original product. However, where the proprietary 66 — Point 8(a)(ii), second paragraph, Article 4 of Directive medicinal product is intended for a different therapeudc use 65/65, as amended by Directive 87/21. from that of the other proprietary medicinal products mar- 67 — Explanatory Memorandum of the Commission, cited above keted or is to be administered by different routes or in dif- at footnote 40, point 15. ferent doses, the results of appropriate pharmacological and 68 — For the purposes of Directive 75/319, as amended by toxicological tests and/or of appropriate clinical trials must Directives 83/570 and 87/19. be provided.'

34. The Court is asked to reply to the fol- lowing question: 35. The national court restricts its request for a ruling to a very specific case and main- tains that the MCA was correct in deciding to use the abridged procedure by detailed references to published scientific literature, in considering Norgine's application for marketing authorization in respect of the 'In Community law is Directive 65/65/EEC medicinal product Unigam. 71 In so far as the to be interpreted as permitting a national legal framework set out above applies to this competent authority in the circumstances of case, Scotia's claim to have been the victim of a case such as the present to issue an autho- rization to place a medicinal product on the market pursuant to an application made under Article 4(8)(a)(ii) of Council Directive 71 — Order for reference, p. 18: '... it would be poindess to remit 65/65/EEC as replaced by Council Directive the application fto the MCA] for a redetermination as to whether exemption (a)(ii) is applicable and in discretion I 87/21/EEC, notwithstanding the fact that would refuse to do so'.

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36. With regard to that specific point, I am doubtful whether the procedure followed by the MCA when considering an application for marketing authorization under the abridged procedure by detailed references to 38. By contrast, the procedure followed by published scientific literature 75 is consistent the MCA ignores the objective specifically with the requirements of Community law. I pursued, favours a secondary objective as am not persuaded that the MCA made at opposed to that specific and mandatory most a mere error of fact in the case in objective, has the effect of emulating the point. 7 6 My misgivings are sustained by national procedures targeted by the Commu- many unanswered questions. For example, nity legislature when it drew up Directive although the national court classes Scotia 87/21 78 and, in a word, renders that measure as an innovative firm,77 at no point is it ineffective. stated that the MCA took account of the law concerning the industrial and commercial

72 — Order of the Divisional Court, p. 3. 73 — The MCA justified its use of the abridged procedure as regards Unigam on the grounds that it had the same con- 39. However, for lack of additional infor- stituent or constituents as Epogam and Efamast (order for reference, p. 13, and Observations of the United Kingdom, mation, and taking into account my terms of point 28). reference in the case before the Court, I shall 74 — The conditions for invoking the principle of non- discrimination have not been satisfied (consistent case-law confine myself to the question asked by the of the Court, especially the judgment in Case 283/83 Rocke v Hauptzollamt Mainz [1984] ECR 3971, paragraph 7). national court. 75 — Point 8(a)(ii), second paragraph, Arricie 4 of Directive 65/65, as amended by Directive 87/21. 76 — Order of the Divisional Court, p. 18. 77 — Order for reference, p. 2. 78 — See above, footnote 40.

45. I maintain that it would be unacceptable to endorse that practice, which is contrary not only to the spirit but also to the letter of that legislation.

43. The MCA decided to grant Norgine 80 — Part II, Chapter I, point B, first paragraph of the annex to the standards and protocols directive, as amended by Direc- marketing authorization for the product tive 87/19: '... a qualitative and quantitative study of the Unigam according to the procedure laid toxic reactions which may result from a single administra- tion of the active substance or substances contained in the down in point 8(a)(ii), second paragraph, proprietary medicinal product, in the proportions and physico-chemical state in which they are present in the Article 4, when the dossier contained n o actual product'. published material 79 referring to single-dose 81 — Part II, Chapter I, point G, first paragraph of the annex to the standards and protocols directive: '... the fate of the active substance within the organism'. 82 — Part III, annex to the standards and protocols directive, clinical trials on volunteers (whether well or ill). 79 — O r d e r for reference, p. 21, and Observations of the United 83 — Observations of the United Kingdom, point 9, and Obser- Kingdom, point 30. vations of the Commission, point 13.

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The the attainment of the ultimate objective licensing authority must ascertain that evi- (expanded single market in quality medicinal dence of the safety, efficacy and quality of products). the constituent or constituents of the medic- inal product for which marketing authoriza- tion is sought has been adduced in com- pliance with the requirements laid down 85 (observance of minimum standards concern- 49. With regard to pharmacodynamic tests, ing control methods and qualifications of Scotia appears not to have submitted the those carrying out the tests 86 ). results. 89 If that is so, it does not mean that the United Kingdom's practice is valid.

75/319? 84 — Explanatory Memorandum of the Commission, cited above at footnote 40, point 15. 85 — Article 11, second paragraph, of Directive 65/65, as amended by Directive 83/570: 'An authorization shall also be suspended or revoked where the particulars supporting the application as provided for in Articles 4 and 4a are 51. Once more the United Kingdom's incorrect or have not been amended in accordance with Article 9a, or when the controls referred to in Article 8 of practice is at variance with Community this directive or in Article 27 of Second Council Directive legislation. 75/319/EEC of 20 May 1975 on the approximation of pro- visions laid down by law, regulation or administrative action relating to proprietary medicinal products have not

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52. It permits the abridged procedure to be 55. I shall not Unger over the question used even where no expert has expressed an whether or not the United Kingdom's prac- opinion as to whether recourse to it is justi- tice of not complying with Article 2(c) is jus- fied 93 and where separate toxicological and tifiable. The letter of the law is, to my mind, pharmacological reports have not been sub- unequivocal. A qualified expert is to carry mitted. 94 out tests and trials and produce analytical reports pursuant to the rules in force 9 8 in order to demonstrate that the medicinal product for which marketing authorization is sought is a generic one. That is one of the conditions governing the acceptability of an application for marketing authorization sub- mitted under the abridged procedure. 53. The United Kingdom does not put for- ward any arguments concerning failure to comply with Article 2(c) of Directive 75/319; on the other hand, as regards Article 2(b) of that directive, it asserts 95 that the primary purpose of Directive 87/21 is to safeguard public health and avoid unnecessary tests. Accordingly, what is required is non- compliance with the substantive rules. 96

56. As regards non-compliance with Article 2(b), I note that the original version 9 9 merely required experts with qualifications

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knowledge. Derogations from the minimum rules laid down can be allowed only on that condition. Where, therefore, scientific progress requires those tests and reports to be submitted separately, an applicant for marketing authorization will have to comply with that further requirement. 59. By adopting the solution I am propos- ing, the Court will be following its own line of decided cases. In two judgments, it held that the authority competent to issue mar- keting authorization may not refuse 101 or provide for the lapse of authorization, 1 0 2 except by reference to overriding require-

. . must be interpreted as meaning that the suspension or revocation 8(a)(ii), second paragraph, Article 4 must, of an authorization to market medicinal products may be decided only on the grounds Uid down in that directive or unless scientifically justified, be refused. other applicable provisions of Community law. 2. Directive 65/65/EEC, as amended, precludes national authorities not only from introducing grounds for suspen- sion or revocation other than those laid down by Commu- nity law but also from providing for the lapse of authori- zations to market medicinal products' (operative part, 100 — Article 1(4) and (6) of Directive 83/570. emphasis added).

— the Clin-Midy and Pierrel cases which require strict compliance with the Com- munity provisions applicable to market- ing authorizations. 106 63. Thus the reasons why the M C A's prac- tice in respect of marketing authorization for medicinal products pursuant to Article 4, 103 — See points 18 to 23 above. second paragraph, point 8(a)(ii) ought not t o 104 — See points 46 to 48 above. be upheld can be grouped together as fol- 105 — See points 24 to 26 and 27 to 30 above. lows: 106 — See points 59 to 62 above.

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64. In conclusion, in the light of the considerations set out above, I propose that the Court give the following answer to the question submitted by the Divisional Court:

Article 4, second paragraph, point (8)(a)(ii) of Council Directive 65/65/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products, as amended by Council Directive 87/21/EEC of 22 December 1986 precludes a national competent authority in circumstances such as those of the present case from issuing an authorization to place a medicinal prod- uct on the market where the particulars and documents submitted in support of such an application do not contain:

(a) detailed references to published scientific literature presented in accordance with each of the requirements laid down in Parts 2 and 3 of the Annex t o Council Directive 75/318/EEC of 20 May 1975 on the approximation of the laws of Member States relating to analytical, pharmaco-toxicological and clin- ical standards and protocols in respect of the testing of proprietary medicinal products; or